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3. Does Applying Subsampling in Quantile Mapping Affect the Climate Change Signal?

Author

Reiter, Philipp and Casper, Markus C.

Subjects
ATMOSPHERIC models, CLIMATE change, SAMPLE size (Statistics), CALIBRATION
Abstract

Bias in regional climate model (RCM) data makes bias correction (BC) a necessary pre-processing step in climate change impact studies. Among a variety of different BC methods, quantile mapping (QM) is a popular and powerful BC method. Studies have shown that QM may be vulnerable to reductions in calibration sample size. The question is whether this also affects the climate change signal (CCS) of the RCM data. We applied four different QM methods without subsampling and with three different subsampling timescales to an ensemble of seven climate projections. BC generally improved the RCM data relative to observations. However, the CCS was significantly modified by the BC for certain combinations of QM method and subsampling timescale. In conclusion, QM improves the RCM data that are fundamental for climate change impact studies, but the optimal subsampling timescale strongly depends on the chosen QM method. [ABSTRACT FROM AUTHOR]

Published
2024
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9. List of contributors

Author

Alves, Lincoln Muniz, primary, Bandala, Erick, additional, Belcher, C., additional, Bruland, Oddbjørn, additional, Caballero García, Lizeth, additional, Calvo, L., additional, Capra Pedol, Lucia, additional, Casper, Markus, additional, Chen, Liding, additional, Costache, Romulus, additional, Daliakopoulos, Ioannis N., additional, de Jesus da Costa Barreto, Naurinete, additional, Dostál, Tomáš, additional, Elliott, A., additional, Fernández, C., additional, Ferreira, Carla S.S., additional, Fischer, Franziska K., additional, Flanagan, Dennis C., additional, Fowler, Hayley, additional, García, L.V., additional, García-Llamas, P., additional, Ghahramani, Afshin, additional, Ghajarnia, Navid, additional, Goonetilleke, Ashantha, additional, Gutiérrez-Hernández, O., additional, Guzmán, Gema, additional, Gyasi-Agyei, Yeboah, additional, Hassan, Hanashriah, additional, Illán-Fernandez, Emilio, additional, Ioana-Toroimac, Gabriela, additional, Iserloh, Thomas, additional, Kalantari, Zahra, additional, Kavka, Petr, additional, Kiani-Harchegani, Mahboobeh, additional, Laburda, Tomáš, additional, Latif, Mohd Talib, additional, Llopart, Marta, additional, López-Vicente, Manuel, additional, Lucas-Borja, Manuel Esteban, additional, Marcos, E., additional, Marzen, Miriam, additional, McGehee, Ryan P., additional, Minea, Gabriel, additional, Mohajerani, Hadis, additional, Najafi, Saeed, additional, Nearing, Mark A., additional, Neumann, Martin, additional, Ohba, Masamichi, additional, Othman, Murnira, additional, Pérez-Morales, Alfredo, additional, Piccolo, María Cintia, additional, Rahmati, Omid, additional, Rodrigo-Comino, Jesús, additional, Rodriguez-Narvaez, Oscar M., additional, Romero-Díaz, Asunción, additional, Ruiz-Sinoga, José Damián, additional, Seifollahi-Aghmiuni, Samaneh, additional, Senciales, José María, additional, Solomun, Marijana K., additional, Srivastava, Puneet, additional, Tudose, Nicu-Constantin, additional, Turcu, Vasile, additional, Vega, J.A., additional, Wei, Wei, additional, Winterrath, Tanja, additional, Yu, Yang, additional, Zema, Demetrio Antonio, additional, and Zumr, David, additional

Published
2021
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10. Finding behavioral parameterization for a 1-D water balance model by multi-criteria evaluation

Author

Casper Markus C., Mohajerani Hadis, Hassler Sibylle, Herdel Tobias, and Blume Theresa

Subjects
forest evapotranspiration, water balance simulation, soil parameterization, behavioral model, Hydraulic engineering, TC1-978
Abstract

Evapotranspiration is often estimated by numerical simulation. However, to produce accurate simulations, these models usually require on-site measurements for parameterization or calibration. We have to make sure that the model realistically reproduces both, the temporal patterns of soil moisture and evapotranspiration. In this study, we combine three sources of information: (i) measurements of sap velocities; (ii) soil moisture; and (iii) expert knowledge on local runoff generation and water balance to define constraints for a “behavioral” forest stand water balance model. Aiming for a behavioral model, we adjusted soil moisture at saturation, bulk resistance parameters and the parameters of the water retention curve (WRC). We found that the shape of the WRC influences substantially the behavior of the simulation model. Here, only one model realization could be referred to as “behavioral”. All other realizations failed for a least one of our evaluation criteria: Not only transpiration and soil moisture are simulated consistently with our observations, but also total water balance and runoff generation processes. The introduction of a multi-criteria evaluation scheme for the detection of unrealistic outputs made it possible to identify a well performing parameter set. Our findings indicate that measurement of different fluxes and state variables instead of just one and expert knowledge concerning runoff generation facilitate the parameterization of a hydrological model.

Published
2019
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11. Adressen

Author

Lammert, Frank, primary, Stallmach, Andreas, additional, Appenrodt, Beate, additional, Bürger, Martin, additional, Casper, Markus, additional, Grotemeyer, Katharina, additional, Krawczyk, Marcin, additional, Prechter, Florian, additional, Rüddel, Jessica, additional, Weber, Marko, additional, and Zeitz, Jonas, additional

Published
2020
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14. Temporal changes in soil water erosion on sloping vineyards in the Ruwer- Mosel Valley. The impact of age and plantation works in young and old vines

Author

Rodrigo-Comino Jesús, Brings Christine, Iserloh Thomas, Casper Markus C., Seeger Manuel, Senciales José M., Brevik Eric C., Ruiz-Sinoga José D., and Ries Johannes B.

Subjects
soil erosion, old vineyard, young vineyard, rainfall, tillage, ruwer-mosel valley, Hydraulic engineering, TC1-978
Abstract

It is well known that rainfall causes soil erosion in sloping German vineyards, but little is known about the effect of age of plantation on soil erosion, which is relevant to understand and design sustainable management systems. In the Ruwer-Mosel valley, young (1- to 4-years) and old (35- to 38-years after the plantation) vineyards were selected to assess soil and water losses by using two-paired Gerlach troughs over three years (2013-2015). In the young vineyard, the overland flow was 107 L m-1 and soil loss 1000 g m-1 in the year of the plantation, and decreased drastically over the two subsequent years (19 L m-1; 428 g m-1). In the old vineyard, soil (from 1081 g m-1 to 1308 g m-1) and water (from 67 L m-1 to 102 L m-1) losses were 1.2 and 1.63 times higher, respectively, than in the young vineyard.

Published
2017
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15. Common variation in FAM155A is associated with diverticulitis but not diverticulosis

Author

Reichert, Matthias C., Kupcinskas, Juozas, Schulz, Antje, Schramm, Christoph, Weber, Susanne N., Krawczyk, Marcin, Jüngst, Christoph, Casper, Markus, Grünhage, Frank, Appenrodt, Beate, Zimmer, Vincent, Tamelis, Algimantas, Lukosiene, Jaune I., Pauziene, Neringa, Kiudelis, Gediminas, Jonaitis, Laimas, Goeser, Tobias, Malinowski, Maciej, Glanemann, Matthias, Kupcinskas, Limas, and Lammert, Frank

Published
2020
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18. Genetic variants in PNPLA3 and TM6SF2 predispose to the development of hepatocellular carcinoma in individuals with alcohol-related cirrhosis

Author

Stickel, Felix, Buch, Stephan, Nischalke, Hans Dieter, Weiss, Karl Heinz, Gotthardt, Daniel, Fischer, Janett, Rosendahl, Jonas, Marot, Astrid, Elamly, Mona, Casper, Markus, Lammert, Frank, McQuillin, Andrew, Zopf, Steffen, Spengler, Ulrich, Marhenke, Silke, Kirstein, Martha M., Vogel, Arndt, Eyer, Florian, von Felden, Johann, Wege, Henning, Buch, Thorsten, Schafmayer, Clemens, Braun, Felix, Deltenre, Pierre, Berg, Thomas, Morgan, Marsha Y., and Hampe, Jochen

Published
2018
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25. Digital single-operator pancreatoscopy for the treatment of symptomatic pancreatic duct stones: a prospective multicenter cohort trial

Author

Gerges, Christian, Albers, David, Schmitz, Lukas, Goni, Elisabetta, Cappello, Annalisa; https://orcid.org/0000-0002-9248-9549, Schirra, Jörg, Casper, Markus, Dormann, Arno J, Hartmann, Dirk, Hollenbach, Marcus, Schneider, Markus, Denzer, Ulrike W, Dechene, Alexander, Dollhopf, Markus, Mayerle, Julia, Schumacher, Brigitte, van Geenen, Erwin-Jan M, Neuhaus, Horst, Siersema, Peter D, Ellrichmann, Mark, Beyna, Torsten, Gerges, Christian, Albers, David, Schmitz, Lukas, Goni, Elisabetta, Cappello, Annalisa; https://orcid.org/0000-0002-9248-9549, Schirra, Jörg, Casper, Markus, Dormann, Arno J, Hartmann, Dirk, Hollenbach, Marcus, Schneider, Markus, Denzer, Ulrike W, Dechene, Alexander, Dollhopf, Markus, Mayerle, Julia, Schumacher, Brigitte, van Geenen, Erwin-Jan M, Neuhaus, Horst, Siersema, Peter D, Ellrichmann, Mark, and Beyna, Torsten

Abstract

BACKGROUND Digital single-operator pancreatoscopy (DSOP)-guided lithotripsy is a novel treatment modality for pancreatic endotherapy, with demonstrated technical success in retrospective series of between 88 % and 100 %. The aim of this prospective multicenter trial was to systematically evaluate DSOP in patients with chronic pancreatitis and symptomatic pancreatic duct stones. METHODS Patients with symptomatic chronic pancreatitis and three or fewer stones ≥ 5mm in the main pancreatic duct (MPD) of the pancreatic head or body were included. The primary end point was complete stone clearance (CSC) in three or fewer treatment sessions with DSOP. Current guidelines recommend extracorporeal shock wave lithotripsy (ESWL) for MPD stones > 5 mm. A performance goal was developed to show that the CSC rate of MPD stones using DSOP was above what has been previously reported for ESWL. Secondary end points were pain relief measured with the Izbicki pain score (IPS), number of interventions, and serious adverse events (SAEs). RESULTS 40 chronic pancreatitis patients were included. CSC was achieved in 90 % of patients (36/40) on intention-to-treat analysis, after a mean (SD) of 1.36 (0.64) interventions (53 procedures in total). The mean (SD) baseline IPS decreased from 55.3 (46.2) to 10.9 (18.3). Overall pain relief was achieved in 82.4 % (28/34) after 6 months of follow-up, with complete pain relief in 61.8 % (21/34) and partial pain relief in 20.6 % (7/34). SAEs occurred in 12.5 % of patients (5/40), with all treated conservatively. CONCLUSION DSOP-guided endotherapy is effective and safe for the treatment of symptomatic MPD stones in highly selected patients with chronic pancreatitis. It significantly reduces pain and could be considered as an alternative to standard ERCP techniques for MPD stone treatment in these patients.

Published
2023

31. SEC62 and SEC63 Expression in Hepatocellular Carcinoma and Tumor-Surrounding Liver Tissue

Author

Casper, Markus, Linxweiler, Maximilian, Linxweiler, Johannes, Zimmermann, Richard, Glanemann, Matthias, Lammert, Frank, and Weber, Susanne N.

Subjects
Hepatocarcinogenesis, Intracellular signaling, Chronic liver disease, Gene expression, Liver tumor, Immunohistochemistry, Liver cancer, Endoplasmic reticulum, Research Article
Abstract

INTRODUCTION: The endoplasmic reticulum transmembrane proteins Sec61, Sec62, and Sec63 are responsible for the intracellular trafficking of precursor proteins and affect intracellular signaling. SEC62 overexpression has been linked to various human cancers. Our aim was to investigate SEC62 and SEC63 expression in hepatocellular carcinoma (HCC) and surrounding liver tissue. PATIENTS AND METHODS: Primary liver tissue was collected from 11 consecutive patients (70 ± 9 years; 10 men) who underwent HCC resection. In the HCC and the tumor-surrounding liver tissue we investigated SEC62 und SEC63 mRNA expression using quantitative real-time PCR. For Sec62, immunohistochemistry was performed. RESULTS: SEC62and SEC63 total mRNA contents were significantly (p = 0.001) higher in HCCs (CT 22.5 ± 0.4 and 22.6 ± 0.3) when compared to the surrounding tissue (CT 24.6 ± 0.6 and 25.1 ± 0.9). Using the comparative CTmethod, SEC62 and SEC63 expression in HCC was increased 5- and 8.1-fold, respectively, in comparison to surrounding tissue. For Sec62 immunohistochemistry, the mean immunoreactive scores (IRS) were 7.9 ± 2.9 for HCC and 4.8 ± 1.2 for non-tumorous liver (p = 0.027). The mean IRS in HCC were 5.7 ± 3.5 and 8.9 ± 2.3 for patients without (n = 3) and with tumor recurrence (n = 8), respectively. CONCLUSIONS: Overexpression of SEC62 and SEC63 is a common feature of HCC. The role of Sec62 as a prognostic marker for tumor recurrence after surgery and its potential role in treatment stratification must be addressed in future studies.

Published
2022
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33. Endoscopic Mucosal Resection of Non-pedunculated Colorectal Polyps ≥20mm: Outcome in a Self-taught Skills Environment.

Author

Casper, Markus, Krawczyk, Marcin, and Lammert, Frank

Subjects
*COLON polyps, *ENDOSCOPIC surgery, *POLYPECTOMY, *POLYPS, *LEARNING, *LEARNING curve, *TUMORS
Abstract

Background & Aims: Endoscopic mucosal resection (EMR) of non-pedunculated colorectal polyps ≥20mm is technically demanding and should preferentially be performed by specialist endoscopists in referral centres. Little is known about the outcome in institutions establishing this competency. Here, we report the learning curve on 100 consecutive large non-pedunculated polyps resected by a single endoscopist with self-taught acquisition of skills. Methods: We analysed data on 100 non-supervised EMR procedures performed at our academic endoscopy centre (2016-2021), representing a single endoscopist's learning curve beginning with the first polyp ≥20 mm. Results: The median polyp size was 30 mm (20-70mm), and 61% of all polyps were ≥30 mm. Predominant polyp morphology was 0-Is (34%) or 0-IIa (47%), and most polyps developed in the ascending colon (36%). In total, 20% of polyps showed high-grade intraepithelial neoplasia, and 8% included pT1 carcinoma. Adenoma recurrence rate after piecemeal resection was 21%. All but one recurrent adenoma were treated endoscopically. Deep mural injury, intra-procedural bleeding and post-procedural bleeding were detected and managed endoscopically in 3%, 21%, and 4% of procedures, respectively. Overall, surgery could be avoided in 91% of all and 98% of nonmalignant polyps. Results for the first 50 polyps did not differ from results for the following polyps. Conclusions: Structured training is advisable to acquire advanced EMR skills. Our data show that autonomous acquisition of skills after finishing a training course represents an acceptable alternative with good results in the setting of an open error culture. Continuous review of outcome parameters and complication rate is mandatory during the learning process. [ABSTRACT FROM AUTHOR]

Published
2023
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34. Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: Results from a genome-wide case-control study

Author

Buch, Stephan, Innes, Hamish, Lutz, Philipp Ludwig, Nischalke, Hans Dieter, Marquardt, Jens U, Fischer, Janett, Weiss, Karl Heinz, Rosendahl, Jonas, Marot, Astrid, Krawczyk, Marcin, Casper, Markus, Lammert, Frank, Eyer, Florian, Vogel, Arndt, Marhenke, Silke, Von Felden, Johann, Sharma, Rohini, Atkinson, Stephen Rahul, McQuillin, Andrew, Nattermann, Jacob, Schafmayer, Clemens, Franke, Andre, Strassburg, Christian, Rietschel, Marcella, Altmann, Heidi, Sulk, Stefan, Thangapandi, Veera Raghavan, Brosch, Mario, Lackner, Carolin, Stauber, Rudolf E, Canbay, Ali, Link, Alexander, Reiberger, Thomas, Mandorfer, Mattias, Semmler, Georg, Scheiner, Bernhard, Datz, Christian, Romeo, Stefano, Ginanni Corradini, Stefano, Irving, William Lucien, Morling, Joanne R., Guha, Indra Neil, Barnes, Eleanor, Ansari, M. Azim, Quistrebert, Jocelyn, Valenti, Luca, Morgan, Marsha Yvonne, Trebicka, Jonel, Berg, Thomas, Deltenre, Pierre, Mueller, Sebastian, Hampe, Jochen, and Stickel, Felix

Subjects
Gastroenterology
Abstract

Objective: Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. Design: Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case-control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). Results: Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-Analysis, at genome-wide significance (p=6.41×10-9, OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10-5, OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12×10-44). Conclusion: This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.

Published
2022

35. Comparison of immersive and non-immersive virtual reality videos as substitute for in-hospital teaching during coronavirus lockdown: a survey with graduate medical students in Germany

Author

Omlor, Albert J., primary, Schwärzel, Leonie S., additional, Bewarder, Moritz, additional, Casper, Markus, additional, Damm, Ellen, additional, Danziger, Guy, additional, Mahfoud, Felix, additional, Rentz, Katharina, additional, Sester, Urban, additional, Bals, Robert, additional, and Lepper, Philipp M., additional

Published
2022
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36. Genetic variation inTERTmodifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study

Author

Buch, Stephan, primary, Innes, Hamish, additional, Lutz, Philipp Ludwig, additional, Nischalke, Hans Dieter, additional, Marquardt, Jens U, additional, Fischer, Janett, additional, Weiss, Karl Heinz, additional, Rosendahl, Jonas, additional, Marot, Astrid, additional, Krawczyk, Marcin, additional, Casper, Markus, additional, Lammert, Frank, additional, Eyer, Florian, additional, Vogel, Arndt, additional, Marhenke, Silke, additional, von Felden, Johann, additional, Sharma, Rohini, additional, Atkinson, Stephen Rahul, additional, McQuillin, Andrew, additional, Nattermann, Jacob, additional, Schafmayer, Clemens, additional, Franke, Andre, additional, Strassburg, Christian, additional, Rietschel, Marcella, additional, Altmann, Heidi, additional, Sulk, Stefan, additional, Thangapandi, Veera Raghavan, additional, Brosch, Mario, additional, Lackner, Carolin, additional, Stauber, Rudolf E, additional, Canbay, Ali, additional, Link, Alexander, additional, Reiberger, Thomas, additional, Mandorfer, Mattias, additional, Semmler, Georg, additional, Scheiner, Bernhard, additional, Datz, Christian, additional, Romeo, Stefano, additional, Ginanni Corradini, Stefano, additional, Irving, William Lucien, additional, Morling, Joanne R, additional, Guha, Indra Neil, additional, Barnes, Eleanor, additional, Ansari, M Azim, additional, Quistrebert, Jocelyn, additional, Valenti, Luca, additional, Müller, Sascha A, additional, Morgan, Marsha Yvonne, additional, Dufour, Jean-François, additional, Trebicka, Jonel, additional, Berg, Thomas, additional, Deltenre, Pierre, additional, Mueller, Sebastian, additional, Hampe, Jochen, additional, and Stickel, Felix, additional

Published
2022
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38. Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results form a genome-wide case-control study

Author

Buch, Stephan, primary, Innes, Hamish, additional, Lutz, Philipp, additional, Nischalke, Hans Dieter, additional, Nattermann, Jacob, additional, Marquardt, Jens U., additional, Fischer, Janett, additional, Weiss, Karl Heinz, additional, Rosendahl, Jonas, additional, Marot, Astrid, additional, Krawczyk, Marcin, additional, Casper, Markus, additional, Lammert, Frank, additional, Eyer, Florian, additional, Vogel, Arndt, additional, Marhenke, Silke, additional, von Felden, Johann, additional, Sharma, Rohini, additional, Atkinson, Stephen, additional, McQuillin, Andrew, additional, Schafmayer, Clemens, additional, Strassburg, Christian, additional, Altmann, Heidi, additional, Sulk, Stefan, additional, Thangapandi, Veera Raghavan, additional, Brosch, Mario, additional, Lackner, Carolin, additional, Stauber, Rudolf E., additional, Canbay, Ali, additional, Link, Alexander, additional, Reiberger, Thomas, additional, Mandorfer, Mattias, additional, Semmler, Georg, additional, Scheiner, Bernhard, additional, Datz, Christian, additional, Romeo, Stefano, additional, Corradini, Stefano Ginanni, additional, Valenti, Luca, additional, Müller, Sascha, additional, Morgan, Marsha, additional, Dufour, Jean-Francois, additional, Trebicka, Jonel, additional, Berg, Thomas, additional, Deltenre, Pierre, additional, Mueller, Sebastian, additional, Hampe, Jochen, additional, and Stickel, Felix, additional

Published
2022
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39. SINGLE-OPERATOR VIDEO PANCREATOSCOPY (SOVP) FOR THE MANAGEMENT OF SYMPTOMATIC PANCREATIC DUCT STONES IN SELECTED CHRONIC PANCREATITIS PATIENTS. A PROSPECTIVE MULTICENTRE COHORT TRIAL

Author

Cappello, Annalisa, primary, Schmitz, Lukas, additional, Albers, David, additional, Rousseau, Matthew, additional, Schirra, Jörg, additional, Goni, Elisabetta, additional, Mayerle, Julia, additional, Casper, Markus, additional, Weismüller, Tobias J., additional, Dormann, Arno J., additional, Hartmann, Dirk, additional, Hollenbach, Marcus, additional, Hampe, Jochen, additional, Kandulski, Arne, additional, Hoffman, Arthur, additional, Schlag, Christoph, additional, Denzer, Ulrike, additional, Arlt, Alexander, additional, Dechene, Alexander, additional, Dollhopf, Markus, additional, Schumacher, Brigitte, additional, Van Geenen, Erwin-Jan M., additional, Siersema, Peter D., additional, Neuhaus, Horst, additional, Ellrichmann, Mark, additional, Beyna, Torsten, additional, and Gerges, Christian, additional

Published
2022
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40. Genetic variation in modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Buch, Stephan, Innes, Hamish, Lutz, Philipp Ludwig, Nischalke, Hans Dieter, Marquardt, Jens U, Fischer, Janett, Weiss, Karl Heinz, Rosendahl, Jonas, Marot, Astrid, Krawczyk, Marcin, Casper, Markus, Lammert, Frank, Eyer, Florian, Vogel, Arndt, Marhenke, Silke, von Felden, Johann, Sharma, Rohini, Atkinson, Stephen Rahul, McQuillin, Andrew, Nattermann, Jacob, Schafmayer, Clemens, Franke, Andre, Strassburg, Christian, Rietschel, Marcella, Altmann, Heidi, Sulk, Stefan, Thangapandi, Veera Raghavan, Brosch, Mario, Lackner, Carolin, Stauber, Rudolf E, Canbay, Ali, Link, Alexander, Reiberger, Thomas, Mandorfer, Mattias, Semmler, Georg, Scheiner, Bernhard, Datz, Christian, Romeo, Stefano, Ginanni Corradini, Stefano, Irving, William Lucien, Morling, Joanne R, Guha, Indra Neil, Barnes, Eleanor, Ansari, M Azim, Quistrebert, Jocelyn, Valenti, Luca, Müller, Sascha A, Morgan, Marsha Yvonne, Dufour, Jean-François, Trebicka, Jonel, Berg, Thomas, Deltenre, Pierre, Mueller, Sebastian, Hampe, Jochen, Stickel, Felix, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Buch, Stephan, Innes, Hamish, Lutz, Philipp Ludwig, Nischalke, Hans Dieter, Marquardt, Jens U, Fischer, Janett, Weiss, Karl Heinz, Rosendahl, Jonas, Marot, Astrid, Krawczyk, Marcin, Casper, Markus, Lammert, Frank, Eyer, Florian, Vogel, Arndt, Marhenke, Silke, von Felden, Johann, Sharma, Rohini, Atkinson, Stephen Rahul, McQuillin, Andrew, Nattermann, Jacob, Schafmayer, Clemens, Franke, Andre, Strassburg, Christian, Rietschel, Marcella, Altmann, Heidi, Sulk, Stefan, Thangapandi, Veera Raghavan, Brosch, Mario, Lackner, Carolin, Stauber, Rudolf E, Canbay, Ali, Link, Alexander, Reiberger, Thomas, Mandorfer, Mattias, Semmler, Georg, Scheiner, Bernhard, Datz, Christian, Romeo, Stefano, Ginanni Corradini, Stefano, Irving, William Lucien, Morling, Joanne R, Guha, Indra Neil, Barnes, Eleanor, Ansari, M Azim, Quistrebert, Jocelyn, Valenti, Luca, Müller, Sascha A, Morgan, Marsha Yvonne, Dufour, Jean-François, Trebicka, Jonel, Berg, Thomas, Deltenre, Pierre, Mueller, Sebastian, Hampe, Jochen, and Stickel, Felix

Abstract

Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case-control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). Associations with variants rs738409 in and rs58542926 in previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41×10, OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10, OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in was associated with an increased leucocyte telomere length (p=2.12×10). This study identifies rs2242652 in as a novel protective factor for HCC in patients with alcohol-related cirrhosis.

Published
2022

41. Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol- related cirrhosis: results from a genome- wide case- control study.

Author

Buch, Stephan, Innes, Hamish, Nischalke, Philipp Ludwig Lutz Hans Dieter, Marquardt, Jens U., Fischer, Janett, Weiss, Karl Heinz, Rosendahl, Jonas, Marot, Astrid, Krawczyk, Marcin, Casper, Markus, Lammert, Frank, Eyer, Florian, Vogel, Arndt, Marhenke, Silke, von Felden, Johann, Sharma, Rohini, and Atkinson, Stephen Rahul

Subjects
GENETIC variation, HEPATOCELLULAR carcinoma, FATTY liver, PROSTATE cancer, CIRRHOSIS of the liver, MOLECULAR biology, GENETIC epidemiology
Published
2023
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44. The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis

Author

Innes, Hamish, Nischalke, Hans Dieter, Guha, Indra Neil, Weiss, Karl Heinz, Irving, Will, Gotthardt, Daniel, Barnes, Eleanor, Fischer, Janett, Ansari, M. Azim, Rosendahl, Jonas, Lin, Shang‐Kuan, Marot, Astrid, Pedergnana, Vincent, Casper, Markus, Benselin, Jennifer, Lammert, Frank, McLauchlan, John, Lutz, Philip L., Hamill, Victoria, Mueller, Sebastian, Morling, Joanne R., Semmler, Georg, Eyer, Florian, von Felden, Johann, Link, Alexander, Vogel, Arndt, Marquardt, Jens U., Sulk, Stefan, Trebicka, Jonel, Valenti, Luca, Datz, Christian, Reiberger, Thomas, Schafmayer, Clemens, Berg, Thomas, Deltenre, Pierre, Hampe, Jochen, Stickel, Felix, Buch, Stephan, UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Service de gastro-entérologie

Subjects
Liver Cirrhosis, Carcinoma, Hepatocellular, Hepatology, Liver Neoplasms, Membrane Proteins, SNP, Genomics, Hepatitis C, Polymorphism, Single Nucleotide, digestive system diseases, ddc, Chronic Liver Disease, Apolipoproteins E, Cirrhosis, Genetics, Humans, Genetic Predisposition to Disease, Liver cancer
Abstract

The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E (APOE), rs2642438 in mitochondrial amidoxime reducing component 1 (MARC1), rs2792751 in glycerol‐3‐phosphate acyltransferase (GPAM), and rs187429064 in transmembrane 6 superfamily member 2 (TM6SF2), previously associated with progressive alcohol‐related and nonalcoholic fatty liver disease, are also associated with HCC. Four HCC case‐control data sets were constructed, including two mixed etiology data sets (UK Biobank and FinnGen); one hepatitis C virus (HCV) cohort (STOP‐HCV), and one alcohol‐related HCC cohort (Dresden HCC). The frequency of each variant was compared between HCC cases and cirrhosis controls (i.e., patients with cirrhosis without HCC). Population controls were also considered. Odds ratios (ORs) associations were calculated using logistic regression, adjusting for age, sex, and principal components of genetic ancestry. Fixed‐effect meta‐analysis was used to determine the pooled effect size across all data sets. Across four case‐control data sets, 2,070 HCC cases, 4,121 cirrhosis controls, and 525,779 population controls were included. The rs429358:C allele (APOE) was significantly less frequent in HCC cases versus cirrhosis controls (OR, 0.71; 95% confidence interval [CI], 0.61‐0.84; P = 2.9 × 10−5). Rs187429064:G (TM6SF2) was significantly more common in HCC cases versus cirrhosis controls and exhibited the strongest effect size (OR, 2.03; 95% CI, 1.45‐2.86; P = 3.1 × 10−6). In contrast, rs2792751:T (GPAM) was not associated with HCC (OR, 1.01; 95% CI, 0.90‐1.13; P = 0.89), whereas rs2642438:A (MARC1) narrowly missed statistical significance (OR, 0.91; 95% CI, 0.84‐1.00; P = 0.043). Conclusion: This study associates carriage of rs429358:C (APOE) with a reduced risk of HCC in patients with cirrhosis. Conversely, carriage of rs187429064:G in TM6SF2 is associated with an increased risk of HCC in patients with cirrhosis.

Published
2022
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46. Variants APOE (rs429358) and TM6SF2 (rs187429064) modify the risk of hepatocellular carcinoma

Author

Innes, Hamish, additional, Nischalke, HansDieter, additional, Weiss, KarlHeinz, additional, Gotthardt, Daniel, additional, Guha, Neil, additional, Barnes, Eleanor, additional, Irving, Will, additional, Fischer, Janett, additional, Rosendahl, Jonas, additional, Casper, Markus, additional, Lammert, Frank, additional, Lutz, PhilipL, additional, Mueller, Sebastian, additional, Semmler, Georg, additional, Eyer, Florian, additional, von Felden, Johann, additional, Link, Alexander, additional, Vogel, Arndt, additional, Marquardt, JensU, additional, Sulk, Stefan, additional, Datz, Christian, additional, Reiberger, Thomas, additional, Schafmayer, Clemens, additional, Berg, Thomas, additional, Hampe, Jochen, additional, Stickel, Felix, additional, and Buch, Stephan, additional

Published
2022
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48. The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis

Author

Innes, Hamish, primary, Nischalke, Hans Dieter, additional, Guha, Indra Neil, additional, Weiss, Karl Heinz, additional, Irving, Will, additional, Gotthardt, Daniel, additional, Barnes, Eleanor, additional, Fischer, Janett, additional, Ansari, M. Azim, additional, Rosendahl, Jonas, additional, Lin, Shang‐Kuan, additional, Marot, Astrid, additional, Pedergnana, Vincent, additional, Casper, Markus, additional, Benselin, Jennifer, additional, Lammert, Frank, additional, McLauchlan, John, additional, Lutz, Philip L., additional, Hamill, Victoria, additional, Mueller, Sebastian, additional, Morling, Joanne R., additional, Semmler, Georg, additional, Eyer, Florian, additional, von Felden, Johann, additional, Link, Alexander, additional, Vogel, Arndt, additional, Marquardt, Jens U., additional, Sulk, Stefan, additional, Trebicka, Jonel, additional, Valenti, Luca, additional, Datz, Christian, additional, Reiberger, Thomas, additional, Schafmayer, Clemens, additional, Berg, Thomas, additional, Deltenre, Pierre, additional, Hampe, Jochen, additional, Stickel, Felix, additional, and Buch, Stephan, additional

Published
2021
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50. Correction: Genetic Variants in PNPLA3 and TM6SF2 Predispose to the Development of Hepatocellular Carcinoma in Individuals With Alcohol-Related Cirrhosis

Author

Stickel, Felix, Buch, Stephan, Nischalke, Hans Dieter, Weiss, Karl Heinz, Gotthardt, Daniel, Fischer, Janett, Rosendahl, Jonas, Marot, Astrid, Elamly, Mona, Casper, Markus, Lammert, Frank, McQuillin, Andrew, Zopf, Steffen, Spengler, Ulrich, Marhenke, Silke, Kirstein, Martha M., Vogel, Arndt, Eyer, Florian, von Felden, Johann, Wege, Henning, Buch, Thorsten, Schafmayer, Clemens, Braun, Felix, Deltenre, Pierre, Berg, Thomas, Morgan, Marsha Y., and Hampe, Jochen

Published
2018
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